| 1. |
- Alexandrov, Ludmil B., et al.
(author)
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Signatures of mutational processes in human cancer
- 2013
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421
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Journal article (peer-reviewed)abstract
- All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
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| 2. |
- Rollauer, Sarah E., et al.
(author)
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Structure of the TatC core of the twin-arginine protein transport system
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7428, s. 210-
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Journal article (peer-reviewed)abstract
- The twin-arginine translocation (Tat) pathway is one of two general protein transport systems found in the prokaryotic cytoplasmic membrane and is conserved in the thylakoid membrane of plant chloroplasts. The defining, and highly unusual, property of the Tat pathway is that it transports folded proteins, a task that must be achieved without allowing appreciable ion leakage across the membrane. The integral membrane TatC protein is the central component of the Tat pathway. TatC captures substrate proteins by binding their signal peptides. TatC then recruits TatA family proteins to form the active translocation complex. Here we report the crystal structure of TatC from the hyperthermophilic bacterium Aquifex aeolicus. This structure provides a molecular description of the core of the Tat translocation system and a framework for understanding the unique Tat transport mechanism.
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| 3. |
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| 4. |
- Kolodner, Elliot K, et al.
(author)
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A cloud environment for data-intensive storage services
- 2011
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In: IEEE third international conference on Cloud computing technology and science (CloudCom), 2011. - : IEEE conference proceedings. - 9781467300902 ; , s. 357-366
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Conference paper (peer-reviewed)abstract
- The emergence of cloud environments has made feasible the delivery of Internet-scale services by addressing a number of challenges such as live migration, fault tolerance and quality of service. However, current approaches do not tackle key issues related to cloud storage, which are of increasing importance given the enormous amount of data being produced in today's rich digital environment (e.g. by smart phones, social networks, sensors, user generated content). In this paper we present the architecture of a scalable and flexible cloud environment addressing the challenge of providing data-intensive storage cloud services through raising the abstraction level of storage, enabling data mobility across providers, allowing computational and content-centric access to storage and deploying new data-oriented mechanisms for QoS and security guarantees. We also demonstrate the added value and effectiveness of the proposed architecture through two real-life application scenarios from the healthcare and media domains.
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| 5. |
- Schuenemann, Verena J., et al.
(author)
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Genome-Wide Comparison of Medieval and Modern Mycobacterium leprae
- 2013
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 341:6142, s. 179-183
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Journal article (peer-reviewed)abstract
- Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons of five medieval leprosy cases from the United Kingdom, Sweden, and Denmark. In one case, the DNA was so well preserved that full de novo assembly of the ancient bacterial genome could be achieved through shotgun sequencing alone. The ancient M. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geographic origins. The comparisons revealed remarkable genomic conservation during the past 1000 years, a European origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers, both DNA and mycolic acids, in ancient skeletons has major implications for palaeomicrobiology and human pathogen evolution.
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